Regulation of autophagy and its impact in the development and progression of hepatocellular cancer.

目的是阐明细胞凋亡和自噬在非酒精性脂肪性肝炎发病机制中的关系，以及在肝细胞癌（HCC）治疗中的作用。过量的游离脂肪酸通过增加内质网应激抑制肝细胞自噬流并诱导细胞凋亡。肝细胞特异性Mcl-1基因敲除小鼠显示，慢性增加的肝细胞凋亡导致肝纤维化和癌症，这表明，在脂肪性肝炎的发病机制中，由自噬损伤诱导的持续肝细胞凋亡有助于肝纤维化和癌变。最后，索拉非尼，一种用于治疗HCC的多激酶抑制剂，增强了自噬活性，从而抑制了肝癌细胞的凋亡。综上所述，自噬在肝癌的发生发展中可能是一把双刃剑，促进促进癌细胞的存活，抑制则促进肿瘤的爆发。

The aim was to clarify the relationship between apoptosis and autophagy in the pathogenesis of non-alcoholic steatohepatitis, and also in the treatment of hepatocellular carcinoma (HCC). Excess free fatty acids suppressed autophagic flux in hepatocytes and induced apoptosis by increasing endoplasmic reticulum stress. Hepatocyte-specific Mcl-1 knockout mice revealed that chronically increased hepatocyte apoptosis leads to liver fibrosis and cancer, suggesting that, in the pathogenesis of steatohepatitis, continuous hepatocyte apoptosis induced by autophagy impairment contributes to hepatic fibrogenesis and carcinogenesis. Finally, sorafenib, a multikinase inhibitor for the treatment of HCC, enhanced autophagic activity, which then inhibited apoptosis in hepatoma cells. In conclusion, autophagy may be a double-edged sword in the liver cancer development and progression; the promotion promotes the survival of the cancer cells while the restraint promotes the outbreak of cancer.